Investigating the Cytotoxicity of Folate-Conjugated Bismuth Oxide Nanoparticles on KB and A549 Cell Lines

Abstract

Purpose: Lately, bismuth-based nanomaterials have been widely utilized in medical researches such as imaging, drug delivery and radio-sensitization. Despite their advantages, bismuth-based compounds have shown toxic effects in humans. There are few studies on cytotoxicity effects of bismuth oxide (Bi2O3) nanoparticles (NPs) in-vitro. In this study, we aimed to investigate cytotoxicity of bare and also folate and 5-aminolevulinic acid (5-ALA)-conjugated Bi2O3 NPs on nasopharyngeal carcinoma (KB) and lung cancer (A549) cell lines.Methods: Bi2O3 NPs were synthesized and conjugated with folate and 5-ALA. KB and A549 cells were cultured and incubated with 10, 20, 50 and 100 μg/ml concentrations of bare and folate-5-ALA-conjugated NPs. The survival rates were obtained after 2 and 24 hours incubation of the cells with NPs using MTT assay. Also, apoptosis and ROS generation induced by the NPs in the treated cells were obtained using Caspases-3 activity assay and flow cytometry analysis, respectively.Results: Bi2O3 NPs were successfully synthesized with average size of 19.2 ± 6.5 nm, then conjugated with 5-ALA and folate. Either naked or folate-conjugated NPs were easily taken up by the cells in a concentration-dependent manner and showed cytotoxic effects. The significant cell death was noted at the concentrations more than 50 μg/ml for both compounds.Conclusion: Results indicated low cytotoxicity of the prepared NPs at lower incubation periods, which is very important for their further applications. However, 24 hours incubation of the cells with both forms of NPs caused more cell killing and the cytotoxicity increased with increasing concentrations of the NPs.

Liposomal Formulation of Snakehead Fish (Ophiocephalus striatus) Powder and Toxicity Study in Zebrafish (Danio rerio) Model

“…The after effects of cytotoxicity screening, accordingly, could choose which materials are to be exposed to a decontamination procedure. 33 Therefore, this needs a concern relating to the toxicity effect of natural compounds. Zebrafish model is one of toxicity tests to determine toxicity effect of materials which is derived from natural products because it is easy to be applied and utilized as important model for understanding the mechanisms of development and diseases such as cancer.…”

Bismuth Oxide Nanoparticles Induced Oxidative Stress-Related Inflammation in SH-SY5Y Cell Line

“…It is well known that oxidative stress plays an important role in many complications such as diabetes, atherosclerosis, cancer as well as aging. Since, NPs may induce excessive ROS production in the nervous system with their ability to cross blood brain barrier, neurodegenerative diseases such as Parkinson and Alzheimer could be a consequence of NP toxicity (Sorg 2004;Schrand et al 2010;Afanas'ev 2011). Ahamed et al (2019 reported oxidative stress mediates the cytotoxic effects of Bi 2 O 3 -NPs in MCF-7 cells.…”

“…Oxidative stress can trigger signalling pathways of MAPK8, and transcription factors such as NF-kB and TNF-α; and finally release of pro-inflammatory cytokines and some critical chemokines (Roach et al 2002;Shishodia and Aggarwal, 2002). Ahamed et al (2019) indicated the role of Bax/Bcl-2 pathway in cell death. Several reports indicated that NPs such as titanium dioxide (Monteiller et al 2007), carbon black (Niwa et al 2008) and crystalline silica (Rao et al 2004) induced strong pro-inflammatory responses; however, in the present study Bi 2 O 3 -NPs induced pro-inflammatory response is evaluated for the first time.…”

Bismuth nanomaterials as contrast agents for radiography and computed tomography imaging and their quality/safety considerations

“…Cytotoxicity was ascribed to the disruption of mitochondrial and lysosomal functions by reactive oxygen species with increased malondialdehyde/8-hydroxydeoxyguanine levels and decreased glutathione levels Mahmoud et al (Chemla et al, 2019). Akbarzadeh et al also demonstrated the cytotoxicity of naked or folate-conjugated Bi 2 O 3 NPs at >50 μg/ml in A549 and KB cells in a concentration-dependent manner (Akbarzadeh et al, 2018). Alternatively, bismuth lipophilic NPs (BisBAL NPs) can selectively prevent MCF-7 breast cancer cell growth, and exposure to BisBAL NPs caused loss of cell membrane integrity and fragmentation of tumor cell DNA, which were genotoxic to breast cancer cells, causing cell apoptosis at 10 μM (Hernandez-Delgadillo et al, 2018).…”